A 500 MHz proton NMR study of the conformation of adriamycin

Abstract

The conformation of adriamycin has been investigated by proton NMR spectroscopy at 500 MHz in D₂O and DMSO. Two-dimensional phase-sensitive COSY spectra are recorded to obtain three-bond and long-range coupling constants and hence torsional angles. Interproton distances are estimated from 2D phase-sensitive NOESY spectra using r(1H-2H) = 2.36 Å as internal reference. Pairs of protons correlated by spin-spin coupling give NOE cross peaks with interproton distances < 3.3 Å. Besides these contacts, several other NOE contacts are observed between protons within ring A and within the daunosamine sugar, and between ring A and the daunosamine sugar. It is also observed that protons 7H, 8axH and 8eqH of ring A are close to protons 1'H, 3'H, 4'H, 5'H and 5'CH₃ of the daunosamine sugar with distances lying in the range 2.40-3.90 Å. The 6OH proton is in the proximity of the 1'H and 3'NH⁺₃ protons of the daunosamine sugar. The NOE contacts 5t'H---8eqH, 5'H---8eqH, 5'CH₃---8axH, 5'CH₃---8eqH and 1'H---7H are found to have a strong influence on the solution conformation of the adriamycin molecule determined on the basis of coupling constants and interproton distances.